Estrogen metabolism in abdominal subcutaneous and visceral adipose tissue in postmenopausal women
Open accessAbstract
Context: In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots. Objective: We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women. Design, Setting, Patients, and Interventions: AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone, estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and reductive 17β-hydroxysteroid dehydrogenase enzymes was measured using radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting enzymes was analyzed by real-time reverse transcription quantitative polymerase chain reaction. Results: Estrone concentration was higher in visceral than subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to estrone, and visceral AT estrone and estradiol concentrations correlated positively with serum E1S. Compared with visceral AT, subcutaneous AT produced more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57 nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol increased with waist circumference (r = 0.65; P = 0.022), and estradiol concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P = 0.005). Conclusions: Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women.
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E2 tends to dominate in people with high gonadal function, while E1 becomes more prevalent as gonadal function declines, as occurs in aging, obesity, PCOS, and post-menopause.
“Thus, E2 tends to dominate in people with high gonadal function, while E1 becomes more prevalent as gonadal function declines, as occurs in aging, obesity, PCOS, and post-menopause (64–66).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [64]
The introductory passage states that E1 is the predominant estrogen in postmenopausal women, and the ‘Estrogen concentrations in AT and in serum’ section reports that visceral adipose-tissue E1 increases with BMI. The paper does not establish the broader E2-to-E1 shift with declining gonadal function across aging, obesity, and PCOS; it studies postmenopausal women, and also reports increased local E2 production with adiposity. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn postmenopausal women, tissue to serum ratios of estrone (E1) and especially estradiol (E2) tend to be higher when compared to premenopausal women.
“In postmenopausal women, tissue to serum ratios of E 1 and especially E 2 tend to be higher when compared to premenopausal women [12,20,21].”
From Adipose tissue estrogen production and metabolism in premenopausal women (2021) · cites this paper as [12]
The Results section, “Estrogen concentrations in AT and in serum” (page not provided), reports that tissue E1 and E2 concentrations exceeded serum concentrations in postmenopausal women. The study sampled only postmenopausal women, so it does not establish that their tissue-to-serum ratios were higher than those of premenopausal women, particularly for E2. (LLM, conf=0.86)
Experimental — accuracy not yet measuredObesity is associated with higher circulating and white-adipose-tissue-derived E1 levels.
“obesity is associated with higher circulating and WAT-derived E1 levels (64, 135–138)”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [64]
The Results (‘Estrogen concentrations in AT and in serum’; page not provided) report that visceral adipose-tissue E1 concentration correlated positively with BMI in postmenopausal women. The Discussion says increasing adiposity relates to higher circulating estrogens and reports correlations between serum and adipose-tissue estrogen concentrations, but does not establish that obesity was associated specifically with higher circulating E1 in this study. The claim also omits the study’s postmenopausal-women qualifier. (LLM, conf=0.84)
Experimental — accuracy not yet measuredVisceral white adipose tissue produces more E1 than subcutaneous white adipose tissue.
“visceral WAT has been reported to produce more E1 than subcutaneous WAT (64).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [64]
The Results section reports higher E1 concentration in visceral than subcutaneous adipose tissue in postmenopausal women (928 vs 706 pmol/kg). Both depots produced E1 from E1S, but the measured activity of that conversion was similar in the two depots. Higher concentration does not establish that visceral tissue produces E1 at a higher rate. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn postmenopausal women, abdominal subcutaneous and visceral adipose tissue convert estrone sulfate (E1S) to estrone (E1) and further to estradiol (E2) through the action of steroid sulfatase (STS) and reductive 17β-hydroxysteroid dehydrogenase (17β-HSD) enzymes.
“We showed in postmenopausal women that abdominal subcutaneous and visceral AT converted E 1 S to E 1 and further on to estradiol (E 2 ) through the action of the steroid sulfatase (STS) and reductive 17βhydroxysteroid dehydrogenase (17β-HSD) enzymes, respectively [12].”
From Adipose tissue estrogen production and metabolism in premenopausal women (2021) · cites this paper as [12]
In premenopausal women, mRNA expression patterns of estrogen-metabolizing enzymes in adipose tissue are very similar to those previously reported in postmenopausal women.
“In premenopausal women, the mRNA expression patterns of estrogen-metabolizing enzymes in AT were very similar to those we have previously reported in postmenopausal women [5,12].”
From Adipose tissue estrogen production and metabolism in premenopausal women (2021) · cites this paper as [12]
In postmenopausal women, reductive 17β-hydroxysteroid dehydrogenase (17β-HSD) activity is higher in subcutaneous compared to visceral adipose tissue.
“In postmenopausal women, the reductive 17β-HSD activity was higher in subcutaneous compared to visceral AT [12].”
From Adipose tissue estrogen production and metabolism in premenopausal women (2021) · cites this paper as [12]
In postmenopausal women, visceral adipose tissue has a higher concentration of estrone (E1) compared to subcutaneous adipose tissue, and estradiol (E2) production increases with increasing visceral adiposity.
“Visceral AT had a higher concentration of E 1 compared to subcutaneous AT, and E 2 production increased with increasing visceral adiposity.”
From Adipose tissue estrogen production and metabolism in premenopausal women (2021) · cites this paper as [12]
In postmenopausal women, waist circumference is associated with increased estradiol (E2) production in visceral adipose tissue.
“Waist circumference was associated with increased E 2 production in subcutaneous AT of premenopausal women whereas in postmenopausal women it was associated with increased E 2 production in visceral AT [12].”
From Adipose tissue estrogen production and metabolism in premenopausal women (2021) · cites this paper as [12]
Subcutaneous white adipose tissue has a higher E2 conversion rate than visceral white adipose tissue.
“subcutaneous WAT has been shown to have a higher E2 conversion rate than visceral WAT (64, 192).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [64]
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- Authors
- Hetemäki, N., Savolainen-Peltonen, H., Tikkanen, M. J., Wang, F., Paatela, H., Hämäläinen, E., Turpeinen, U., Haanpää, M., Vihma, V., & Mikkola, T. S.
- Affiliations
- University of Helsinki (FI)
- Helsinki University Hospital (FI)
- Corresponding author
- Mikkola, Tomi S
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2017-09-29
- Volume
- 102
- Issue
- 12
- Pages
- 4588-4595
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2760456888
- Cited by
- 140
- References
- 43
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 22 · 2023: 17 · 2022: 21 · 2021: 11 · 2020: 17 · 2019: 14 · 2018: 5
- FWCI
- 6.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Samfundet Folkhälsan
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- estrogen metabolism, visceral adipose tissue, subcutaneous adipose tissue, postmenopausal women, estrone, estradiol, estrone sulfate, steroid sulfatase, 17β-hydroxysteroid dehydrogenase, HSD17B7, adipose tissue depots, adiposity, waist circumference, body mass index
- MeSH terms
- Aged, Aged, 80 and over, Estradiol, Estrogens, Estrone, Female, Humans, Middle Aged, RNA, Messenger, 17-Hydroxysteroid Dehydrogenases, Postmenopause, Steryl-Sulfatase, Subcutaneous Fat, Intra-Abdominal Fat, Abdominal Fat, Waist Circumference
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